Several infections are successfully combated by the immune system of a mammal such as a human being. However, in some instances, bacteria, fungi, or viruses are not always cleared, which may cause localised or generalised acute infections. This is a serious concern at perinatal-, burn, or intensive care units, and in immunocompromised individuals. Localized acute infections give rise to extensive morbidity. For example, Pseudomonas aeruginosa is a major cause of severe bacterial keratitis and the infection is difficult to treat successfully with the current antimicrobial agents. In other cases, a continuous bacterial persistence at epithelial surfaces may cause or aggravate chronic disease. In humans, this is exemplified by, chronic skin ulcers, atopic dermatitis and other types of eczema, acne, or genitourinary infections. For example, there is now considerable evidence that colonization or infection with the Gram-positive bacterium Staphylococcus aureus is a triggering or exacerbating factor in atopic dermatitis. Approximately 90% of all atopic dermatitis patients are colonized or infected by S. aureus whereas only 5% of healthy individuals harbour that bacterium. Chronic ulcers are colonized or infected by various bacteria, such as P. aeruginosa, and S. aureus, leading to healing delay of these ulcers.
Symptomatic infections may, be treated by various medicaments. Some diseases may also be combated by for instance vaccines. However, vaccines are not always the best treatment option and for certain microorganisms no vaccine is available. When no protection is available treatment of the disease is pursued. Often the treatment is performed by the use of an antibiotic agent, which kills the microbe. However, during the last years several microbes have become resistant against anti-biotic agents. Most likely, resistance problems will increase in the near future. Additionally, several individuals have developed allergy against the antibiotic agent, thereby reducing the possibility to effectively use certain antibiotic agents.
Epithelial surfaces of various organisms are continuously exposed to bacteria. During recent years the innate immune system, based on antibacterial peptides has been attributed important roles in the initial clearance of bacteria at biological boundaries susceptible to infection (Lehrer, R. I., and Ganz, T. (1999) Curr Opin Immunol 11: 23-27, Boman, H. G. (2000) Immunol. Rev. 173, 5-16). Antimicrobial peptides are generally thought to kill bacteria by permeating their membranes, and thus the lack of a specific molecular microbial target minimises resistance development.
Several antimicrobial peptides and proteins, unrelated to the herein, described peptides are known in the art.
U.S. Pat. No. 6,503,881 disclose cationic peptides being an indolicidin analogue to be used as an antimicrobial peptide. The cationic peptides being derived from different species, including animals and plants.
U.S. Pat. No. 5,912,230 disclose anti-fungal and anti-bacterial histatin-based peptides. The peptides being based on defined portions of the amino acid sequences of naturally occurring human histatins and methods for treatment of fungal and bacterial infections.
U.S. Pat. No. 5,717,064 disclose methylated lysine-rich lytic peptides. The lytic peptides being tryptic digestion resistant and non-natural. The lytic peptides are suitable for in vivo administration.
U.S. Pat. No. 5,646,014 disclose an antimicrobial peptide. The peptide was isolated from an antimicrobial fraction from silkworm hemolymph. The peptide exhibits excellent antimicrobial activity against several bacterial strains, such as Escherichia coli, Staphylococcus aureus and Bacillus cereus. 
WO2004016653 discloses a peptide based on the 20-44 sequence of azurocidin. This peptide contains a loop structure linked by disulfide bridges.
U.S. Pat. No. 6,495,516 and related patents, disclose peptides based on the bactericidal 55 kDa protein bactericidal/permeability increasing protein (BPI). The peptides exerted antimicrobial effects as well as had LPS-neutralising capacity.
WO 01/81578 discloses numerous sequences encoding G-coupled protein-receptor related polypeptides, which may be used for numerous diseases.
At present, over 700 different antimicrobial peptide sequences are known (www.bbcm.univ.trieste.it/˜tossi/search.htm), including cecropins, defensins magainins and cathelicidins.
Even though there are a relatively large number of antimicrobial peptides available today there is still an increased need of new improved antimicrobial peptides, which can be used to combat microbes, microbes which are resistant or tolerant against antibiotic agents and/or other antimicrobial agents. More importantly, there is a need for new antimicrobial peptides, which are non-allergenic when introduced into mammals such as human beings.
Due to potential lytic as well as other properties of AMPs against bacterial as well as mammalian membranes, one of the challenges in designing new peptides relies on developing AMPs with high specificity against microorganisms such as bacterial or fungal cells, i.e., a high therapeutic index (minimal hemolytic concentration/minimal antimicrobial activity; MHC/MEC).
Various bacteria, such as P. aeruginosa, E. faecalis, Proteus mirabilis, Streptococcus pyogenes and S. aureus all secrete proteases that degrade several antimicrobial peptides, such as the cathelicidin LL-37. Thus, protease resistant antimicrobial peptides are advantageous from a theraputical standpoint. Additionally, many of the antimicrobial peptides are not very efficient in challenging microorganisms such as bacteria, e.g., S. aureus and P. aeruginosa, frequently playing key roles in problematic patogeneses, and needs to be optimised to show an increased effect.